Study the polymorphism of CYP3A5 and CYP3A4 loci in Iranian population with laryngeal squamous cell carcinoma.
ABSTRACT Cancer reflects a complicated network of interactions between genes and environmental factors. Cytochrome P450 (CYP) is a multi-gene superfamily participating in the metabolism of xenobiotics. The aim of our study was to examine whether polymorphisms in the CYP enzyme genes affect the risk of developing larynx squamous cell carcinoma (SCC). Polymorphism of CYP3A5 and CYP3A4 genes were investigated in 50 patients with laryngeal SCC and 100 control subjects by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP). In patients the CYP3A5 3/3 and 1/3genotypes were detected in 92% and 8% respectively. There was no relation between genotype, allele frequency and grade/stage of tumor. In control group, the frequency of CYP3A5 3/3 and CYP3A5 1/3 genotype were 98% and 2% respectively. There was no significant difference in genotype and allele frequency of this gene between patient and control group. In respect of CYP3A41A/B, people in both patient and control groups had the same genotype of CYP3A41A/1A. In this study, the CYP gene variants were not associated with increased risk of laryngeal SCC. Study on the other genetic factors which are involved in activation/detoxication of procarcinogenes, such as CYP1A1, CYP1B1, CYP2E1 and gluthation S transferase is recommended.
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ABSTRACT: The rate of direct smoking, second hand smoking, and smokeless tobacco users as well as the amount of environmental pollutant like polycyclic aromatic hydrocarons is increasing in Bangladesh. Therefore, the prevalence of lung cancer is increasing day by day. To the best of our knowledge, no pharmacogentic study of CYP3A4, CYP3A5 genes has been reported on Bangladeshi population relating those with lung cancer. The present study was conducted to determine the association of CYP3A4, CYP3A5 gene polymorphisms and tobacco smoking in the development of lung cancer in Bangladeshi population. A case–control study was carried out on 106 lung cancer patients and 116 controls to investigate three allelic variants—CYP3A4*1B, CYP3A5*3, and CYP3A5*6 using Polymerase Chain Reaction Restriction Fragment Length Polymorphism. Risk of lung cancer was estimated as odds ratio (OR) and 95 % confidence interval (CI) using unconditional logistic regression models. The variant allele frequencies for CYP3A4*1B (*1A/*1B + *1B/*1B) were 2.83 % and 0.86 % and that of CYP3A5*3 (*1A/*3 + *3/*3) were 88.68 % and 85.34 % in cases and controls, respectively. Individual carrying at least one variant allele of CYP3A4*1B (CYP3A4*1A/1B + *1B/1B) has a 3.35 times more risk (OR = 3.35, 95 % Cl = 0.34-32.71, p = 0.271) for developing lung cancer whereas individual carrying at least one variant allele of CYP3A5 (CYP3A5*1A/3 + *3/3) has a 1.26 times more risk (OR = 1.35, 95 % Cl = 0.61–2.97) and both are statistically non-significant (p > 0.05). CYP3A5*6 was absent in the study population. No association of lung cancer with the mentioned polymorphisms was found both in heavy and light smokers. In the cases of all three major types of lung cancer—squamous cell carcinoma, adenocarcinoma, and small cell carcinoma—significantly strong relationships (p ˂ 0.05) have been found. To confirm the association of lung cancer with the mentioned polymorphisms, large number volunteers (patients and controls) will be required.Tumor Biology 10/2013; · 2.52 Impact Factor
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ABSTRACT: Objective: To investigate the relationship between development of laryngeal cancer and the presence of polymorphisms of the MnSOD Val16Ala, CAT-262 C < T and GPx1 Pro198Leu genes in a smoking population. Patients and methods: Single nucleotide polymorphisms were determined in DNA from the peripheral blood erythrocytes of 48 heavy smokers (25 patients with laryngeal cancer and 23 cancer-free controls), using polymerase chain reaction. Results: There were no significant differences in age, smoking duration or smoking intensity, comparing the two groups. The homozygous AA genotype of MnSOD Val16Ala was significantly more prevalent in the cancer group than the control group (92 vs 13 per cent, respectively), while the heterozygous AV genotype of MnSOD Val16Ala was more prevalent in the control group than the cancer group (87 vs 8 per cent, respectively) (p < 0.001). There were no significant differences between the cancer and control groups regarding GPx1 Pro198Leu or CAT-262 C < T polymorphisms. Conclusion: Polymorphism of the MnSOD Val16Ala gene may contribute to susceptibility to laryngeal cancer among smokers.The Journal of Laryngology & Otology 10/2013; 127(10):997-1000. · 0.68 Impact Factor
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ABSTRACT: Previously published data on the association between CYP3A4 A392G and CYP3A5 Met235Thr polymorphisms and the risk of cancer remained controversial. Thus, we performed a meta-analysis to investigate the association between cancer susceptibility and CYP3A4 A392G (18,629 cases and 22,323 controls from 49 studies) and CYP3A5 Met235Thr polymorphisms (14,334 cases and 18,183 from 39 studies) in different inheritance models. We used odds ratios with 95 % confidence intervals to assess the strength of the association. Overall, significant association was found between CYP3A4 A392G polymorphism and cancer susceptibility (dominant model, odds ratio (OR) = 1.19; 95 % confidence interval (CI) = 1.03-1.38). In the further stratified and sensitivity analyses, significant increased prostate cancer risk was found among Caucasians (dominant model, OR = 1.88; 95 % CI = 1.20-2.95; recessive model, OR = 2.10; 95 % CI = 1.23-3.60; additive model, OR = 1.80, 95 % CI = 1.24-2.63; homozygous model, OR = 2.34, 95 % CI = 1.36-4.03; heterozygote model, OR = 1.79, 95 % CI = 1.11-2.89) for CYP3A4 A392G. For CYP3A5 Met235Thr polymorphism, no significant association was found among overall analysis and any subgroup analysis. In summary, this meta-analysis suggests that CYP3A4 A392G polymorphism is associated with increased prostate cancer risk among Caucasians and CYP3A5 Met235Thr polymorphism is not associated with the risk of cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 07/2014;